A novel series of potent and selective PDE5 inhibitors with potential for high and dose-independent oral bioavailability

CMN Allerton, CG Barber, KC Beaumont…

Index: Allerton, Charlotte M. N.; Barber, Christopher G.; Beaumont, Kevin C.; Brown, David G.; Cole, Susan M.; Ellis, David; Lane, Charlotte A. L.; Maw, Graham N.; Mount, Natalie M.; Rawson, David J.; Robinson, Colin M.; Street, Stephen D. A.; Summerhill, Nicholas W. Journal of Medicinal Chemistry, 2006 , vol. 49, # 12 p. 3581 - 3594

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Citation Number: 27

Abstract

Sildenafil (5-[2-ethoxy-5-(4-methyl-1-piperazinylsulfonyl) phenyl]-1-methyl-3-n-propyl-1, 6- dihydro-7 H-pyrazolo [4, 3-d] pyrimidin-7-one), a potent and selective phosphodiesterase type 5 (PDE5) inhibitor, provided the first oral treatment for male erectile dysfunction. The objective of the work reported in this paper was to combine high levels of PDE5 potency and selectivity with high and dose-independent oral bioavailability, to minimize the impact on ...